The development in our laboratory of a rapid quantitative method for purification of aldose reductase to homogeneity from single bovine or human lens or a few pooled rat lenses, allows us to look at a whole spectrum of new possibilities regarding the pathogenesis of disease associated with aldose reductase, particularly diabetic cataract. The quantity and properties of aldose reductase and other factors that may be changed in cataracts that would kinetically alter the efficiency of aldose reductase, such as the relative concentration of the oxidized and reduced forms of the coenzyme involved, NADP ion and NADPH will be measured. The absolute amount of the enzyme and the physical and kinetic constants will also be monitored during cataract formation in the experimental rats, at times sequence i.e. beginning cataract stage, intermediate cataract, and complete opacity. Changes in the physical and kinetic constants would yield data that will tell if kinetic alterations of the enzyme protein occur during cataract formation. No significant efforts have been directed toward determination of the quantity and characteristics of the enzyme despite the distinct possibility that kinetic alterations of the enzyme protein may be the primary cause of sugar alcohol accumulation and cataracts. Since aldose reductase is the initial step in the sorbitol pathway, it is likely that regulation of this enzyme is a critical determinant in sugar alcohol production.